Amelogenesis imperfecta (AI) is a heterogeneous group of hereditary disorders affecting primarily the enamel of teeth. Current classification delineates 14 specific AI types based on clinical, histological and hereditary criteria. Abnormal enamel development in AI is thought to result from defective processes involving enamel deposition (hypoplastic AI), initial mineral deposition (hypocalcified AI), and enamel maturation (hypomaturation AI). The specific pathological processes, however, remain to be defined for all the AI types and there continues to be considerable controversy concerning overlap between the different AI groups. Little is known concerning the biochemical and histological abnormalities associated with the distinct AI types. At present only one AI type has been linked to a specific gene locus and only one report exists in the literature concerning the enamel proteins in AI teeth. In order to characterize and understand the AI disorders it is essential that future research include the biochemical analysis of affected tissues so that they may be appropriately classified and the pathological processes elucidated. The specific aim of this investigation is to provide a detailed study of both the biochemical composition and histological appearance of AI enamel. Teeth collected from individuals representing the major AI groups and from age matched normal healthy individuals to serve as controls will be analyzed. A total of 25 AI cases will be evaluated in this investigation. AI kindreds will be evaluated clinically and pedigrees constructed to help determine mode of inheritance. The teeth will be evaluated using light microscopy, scanning electron microscopy and transmission electron microscopy providing a detailed histological interpretation of the AI defects. Biochemical analyses will include evaluating the quantity and character of the enamel proteins using amino acid analysis and SDS PAGE. The mineral composition will be quantified by measuring the mineral per. volume giving accurate determinations of Ca and P while taking into account the tissue porosity. The use of microdissection and conservative histological preparation techniques allows all histological and biochemical analyses to be conducted on each tooth. These methods are thus ideal for providing direct comparisons of histological and biochemical results for each tooth as well as for groups of teeth. Comparisons will be made within and between AI groups to determine variation in expressivity and to establish which clinical, histological and biochemical characteristics are most useful in delineating specific AI types. The immediate goal of this research is to obtain quantitative biochemical data on the different types of AI in order to provide objective characterization. This study will serve as a preliminary investigation used for obtaining baseline data and establishing a data base while additional cases are gathered to ultimately provide a comprehensive evaluation of these diverse hereditary enamel disorders. Knowledge gained from this research :.will lead to specific criteria useful in the diagnosis and differentiation of the AI disorders. The long range goal of this project is to understand the normal and pathological development of human enamel and to definitively delineate the different AI types.